PfHMGB2 has a role in malaria parasite mosquito infection

Abstract

Differentiation of asexually replicating parasites into gametocytes is critical for successful completion of the sexual phase of the malaria parasite life cycle. Gametes generated from gametocytes fuse to form a zygote which differentiates into ookinetes and oocysts. The sporozoites are formed inside oocysts which migrate to the salivary glands for next cycle of human infection. These morphologically and functionally distinct stages require stage-specific gene expression via specific transcriptional regulators. The capacity of high mobility group box (HMGB) proteins to interact with DNA in a sequence independent manner enables them to regulate higher order chromosome organization and regulation of gene expression. Plasmodium falciparum HMGB2 (PfHMGB2) shows a typical L- shaped predicted structure which is similar to mammalian HMG box proteins and shows very high protein sequence similarity to PyHMGB2 and PbHMGB2. Functional characterization of PfHMGB2 by gene deletion (Pfhmgb2¯) showed that knockout parasites develop normally as asexual stages and undergo gametocytogenesis. Transmission experiments revealed that Pfhmgb2¯ can infect mosquitoes and develop as oocyst stages. However, transmission was reduced compared to wild type (WT) parasites and as a consequence, the salivary gland sporozoites were reduced in number. In summary, we demonstrate that PfHMGB2 has no role in asexual growth and a modest role in sexual phase development and parasite transmission to the mosquito.

A single cell atlas of sexual development in Plasmodium falciparum

“…FD3 and MD4/PfARID show a high degree of connectivity to the female and male clusters, respectively, and play a role in gametocyte fertility in P. berghei and P. falciparum (10,28,35,36). Disruption of HMGB2, AP2-O3, and PF3D7_0522900 leads to reduced growth in the ookinete or oocyst stages, indicating that downstream players of these factors may affect transmission (37)(38)(39)(40)(41). Finally, we find an association of the male cluster and AP2-G5, which is known to regulate AP2-G and is essential for gametocyte maturation (1,42).…”

A single cell atlas of sexual development inPlasmodium falciparum

“…FD3 and MD4/PfARID show a high degree of connectivity to the female and male clusters respectively, and play a role in gametocyte fertility in P. berghei and P. falciparum (23,24,32). Disruption of HMGB2, AP2-O3 and PF3D7_0522900 exhibit reduced growth in the ookinete or oocyst stages, indicating that downstream players of these factors may affect transmission (33)(34)(35)(36)(37).…”

Transcriptomic approaches for identifying potential transmission blocking vaccine candidates in Plasmodium falciparum: a review of current knowledge and future directions

“…While the HMGB may not be essential for the parasite to complete its sexual cycle, it may still be critical for its transmission to a new host. While HMGB2 is involved in male fertility and spermatogenesis in turtles, it is not essential for Plasmodium male gamete development (Kumar and Kappe 2022 ). Analysis of RNA-Seq data (Fig.…”